The study reveals that an Ang-(1-7)-related mechanism plays a key role in mediating the potentiation of bradykinin-induced vasodilation by ACE inhibitors.
In the present study, we investigated the potentiating effect of angiotensin-(1-7) Ang-(1-7) on bradykinin (BK)-induced vasodilation in the mesenteric vascular bed of anesthetized spontaneously hypertensive rats using intravital microscopy. Topical application of BK and Ang-(1-7) induced vasodilation in mesenteric arterioles. The BK-induced effect, but not acetylcholine, sodium nitroprusside, or histamine responses, was potentiated in the presence of Ang-(1-7). This interaction was abolished by BK-B(2) and Ang-(1-7) antagonists (HOE 140 and A-779, respectively), a K(+) channel blocker (tetraethylammonium), and cyclooxygenase inhibitors (indomethacin and diclofenac); however, nitric oxide synthase inhibition (Nomega-nitro-L-arginine methyl ester) did not modify the Ang-(1-7)-potentiating activity. Long-term angiotensin-converting enzyme (ACE) inhibition increased BK and Ang-(1-7)-induced vasodilation. The BK potentiation by Ang-(1-7) was preserved after ACE inhibition, Ang II type 1 receptor blockade, or the combination of both treatments. The most striking finding of this study was the unexpected observation that the potentiation of BK vasodilation in spontaneously hypertensive rats treated short- or long-term with ACE inhibitors was reverted by the Ang-(1-7) antagonist A-779. Our results unmasked a key role for an Ang-(1-7)-related mechanism in mediating BK potentiation by ACE inhibitors.
Fernandes et al. (2001) studied this question.